Bleomycin is a first-line chemotherapeutic agent used in the treatment of nonseminomatous testicular cancer.1 One of the most severe adverse effects of bleomycin therapy is pulmonary toxicity, which is thought to be in part caused by free radical-induced oxidative damage2 and can rapidly lead to death.3 High-dose corticosteroids are typically the treatment of choice.4 When this therapy fails, there are very few therapeutic options. Attempts to use a variety of other medications, which are often used in the treatment of pulmonary fibrosis, have had limited success.5 We report a patient with bleomycin pulmonary toxicity (BPT) treated with a protective oxygenation and ventilation strategy, while supported on veno-venous extracorporeal membrane oxygenation (ECMO).
A 45-year-old man with nonseminomatous testicular cancer underwent chemotherapy treatment, which included bleomycin. One week after the completion of his chemotherapy, the patient presented to an outside hospital with a complaint of worsening dyspnea, which was treated with empiric antibiotics for presumed pneumonia. Despite subsequent negative cultures, his respiratory status continued to deteriorate. His worsening hypoxia necessitated intubation for respiratory failure, progressing to acute respiratory distress syndrome. Upon transfer to our facility, a chest computed tomography (CT) demonstrated diffuse consolidation and interstitial infiltrates (Fig. 1), and a bronchoscopic biopsy revealed bronchial mucosa with chronic inflammation and squamous metaplasia, both consistent with a diagnosis of BPT. Despite aggressive treatment with high-dose steroids for 2 weeks, the patient remained on high-frequency ventilation with mean PaO2 of 80 mm Hg, PaCO2 of 60 mm Hg, and FIO2 of 70%. At that time, because of deteriorating gas exchange and an increasing FIO2 requirement, he also required continuous paralysis in an effort to optimize oxygenation. At this time, repeat cultures all remained negative. On hospital day 15, cardiac surgery was consulted for ECMO because of the inability to adequately oxygenate the patient with conventional measures. The patient was advanced to ECMO using a bicaval dual-lumen, single cannula system.
After the initiation of the veno-venous ECMO, mechanical ventilation was weaned rapidly, only requiring a FIO2 of 35% with a positive end-expiratory pressure (PEEP) of 10 mm Hg by ECMO day 1 and a PEEP of 5 mm Hg by ECMO day 2. The patient was extubated on ECMO day 3. Unfortunately, on ECMO day 7, he required reintubation for new-onset multidrug-resistant pseudomonas aeruginosa pneumonia. With antibiotic therapy, the patient progressively improved, and after progressively improving tidal volumes and oxygenation on ventilator FIO2 of 40% and PEEP of 8, the ECMO was weaned by progressively decreasing the ECMO FIO2 and then the sweep gas flow until the circuit was recirculating only. The patient was then successfully decannulated on ECMO day 16. He subsequently required a tracheostomy but was off mechanical ventilation by hospital day 36. He was successfully discharged from the hospital and is currently doing well at home.
Bleomycin is an antitumor antibiotic isolated from Streptomyces verticillus. Because it causes little myelosuppression, it is commonly used in combination with various other cytotoxic chemotherapeutic agents. The mechanism of action of bleomycin is via the production of superoxide free radicals. As a result, its major forms of toxicity are found in the skin and lungs, where the highest oxygen concentrations are present. This may help explain why patients with BPT generally do so poorly once they require a high FIO2 support on the ventilator.6 The incidence of BPT ranges widely from 0% to 46%, with mortality reported as high as 27%.2,7 There has been some promise with high-dose steroids in these patients.8 This was attempted in our patient but was unfortunately unsuccessful. Although many other therapeutic agents9 have been tested successfully in animal models, few options are currently clinically available for this disease process.
Although the use of ECMO for severe lung disease is not a new idea,10 based on the pathophysiology in this case, it seemed particularly appropriate to allow lung healing with minimal ventilator FIO2. We used a single cannula via the right internal jugular vein that, in other patients, has allowed ambulation and even aggressive rehabilitation during recovery of lung function. However, in this patient, we were unable to achieve ambulation secondary to severe weakness and deconditioning, likely contributed to by prolonged paralysis with high-dose steroids.
This report of a patient having acute BPT, successfully treated with protective oxygenation and ventilation support, while supported with veno-venous ECMO, may represent a future role of the utility of ambulatory ECMO for lung healing and warrants further study.
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